Several enzyme systems, including homocysteine methyltransferase and methylmalonyl-CoA mutase, are dependent upon the coenzyme vitamin B12. The function of vitamin B12 has been linked to the cleavage of the Co-alkyl bond. Experimental studies using model systems suggest that the Co-C homolysis is enhanced by steric and/or electronic interactions induced by the trans axial ligand or cis steric interactions resulting from ruffling in the corrin macrocycle. Structural changes in the enzyme and cofactor which trigger Co-C homolysis are of considerable interest. The purpose of this research project is to use modern theoretical techniques to explore the axial ligand effects and the unique structural and conformational properties of very realistic models of the coenzyme vitamin B12. The approximate ab initio molecular orbital method PRDDO will be used to calculate the geometries and conformational preferences in derivatives of vitamin B12. Structural features which affect Co-C homolysis, such as lengthening of the Co-C bond distance, will be calculated. Various R groups will be examined, including R=CN, CH3, and 5'deoxyadenosyl. Initially, calculations will be done on the cobaloxime model systems, where the 5,6-dimethylbenzimidazole moiety is substituted with axial ligands of varying electronic and steric character (L=CN, CH3, py, 2-NH2py, NH3, and 5,6=dimethylbenzimidazole). PRDDO will then be used to calculate steric and electronic effects of the trans axial ligand in a more realistic model which includes the corrin macrocycle. These calculations will represent the highest level theoretical study to date of the electronic and geometrical structures of very realistic models of vitamin B12 and related systems.